We propose to determine whether and how one of the Borrelia burgdorferi surface exposed proteins, Lmp1, functions as a molecular trigger for the induction of host inflammatory responses. Arthritis is one of the most frequent clinical complications of Lyme borreliosis, which results from the infection with the bacterial pathogen Borrelia burgdorferi. Without proper treatment, arthritis is manifested in approximately 60% of the infected patients. A severe infiltration of the inflammatory cells (mostly neutrophil) is a majr feature of Lyme arthritis that contributes to severe pathological damage in the infected joint. Previous studies have demonstrated that B. burgdorferi possesses potent cytokine-stimulating properties and that spirochete lipoproteins induce the production of pro-inflammatory cytokines. Our recent studies involving one of the B. burgdorferi gene products showed that the antigen Lmp1, also annotated as surface-located membrane protein 1, is a virulence determinant of the Lyme disease pathogen. The presence of Lmp1 assists the spirochete to evade host adaptive immune responses. Our preliminary data suggests that although Lmp1-deficient B. burgdorferi persists in severe combined immunodeficient (SCID) mice, unlike wild type spirochetes, these isogenic mutants are unable to induce severe disease. We hypothesize that Lmp1 could contribute to host inflammatory responses subsequently leading to the complications of Lyme borreliosis. The goal of this proposal is to study the potential role of Lmp1 as a molecular trigge of host inflammatory responses. This study will provide new insights into the pathogenesis of Lyme borreliosis and help developing preventive measures against Lyme arthritis. PUBLIC HEALTH RELEVANCE: Lyme borreliosis is an inflammatory disorder caused by the pathogen Borrelia burgdorferi during infection susceptible mammalian hosts, including humans. We propose to characterize the function of a surface-exposed virulence determinant of B. burgdorferi, which is critical for pathogen persistence and the genesis of diseases. This information will contribute to our understanding of molecular adaptation of pathogen in the host and the development of preventive measures against Lyme borreliosis.